Inflammatory proteomics profiling for prediction of incident atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) has emerged as a common condition in older adults. Cardiovascular risk factors only explain about 50% of AF cases. Inflammatory biomarkers may help close this gap as inflammation can alter atrial electrophysiology and structure. This study aimed to determine a cytokine biomarker profile for this condition in the community using a proteomics approach. METHODS: This study uses cytokine proteomics in participants of the Finnish population-based FINRISK cohort studies 1997/2002. Risk models for 46 cytokines were developed to predict incident AF using Cox regressions. Furthermore, the association of participants' C reactive protein (CRP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations with incident AF was examined. RESULTS: In 10 744 participants (mean age of 50.9 years, 51.3% women), 1246 cases of incident AF were observed (40.5% women). The main analyses, adjusted for participants' sex and age, suggested that higher concentrations of macrophage inflammatory protein-1ß (HR=1.11; 95% CI 1.04, 1.17), hepatocyte growth factor (HR=1.12; 95% CI 1.05, 1.19), CRP (HR=1.17; 95% CI 1.10, 1.24) and NT-proBNP (HR=1.58; 95% CI 1.45, 1.71) were associated with increased risk of incident AF. In further clinical variable-adjusted models, only NT-proBNP remained statistically significant. CONCLUSION: Our study confirmed NT-proBNP as a strong predictor for AF. Observed associations of circulating inflammatory cytokines were primarily explained by clinical risk factors and did not improve risk prediction. The potential mechanistic role of inflammatory cytokines measured in a proteomics approach remains to be further elucidated.

Bacterial modification of the host glycosaminoglycan heparan sulfate modulates SARS-CoV-2 infectivity

The human microbiota has a close relationship with human disease and it remodels components of the glycocalyx including heparan sulfate (HS). Studies of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike protein receptor binding domain suggest that infection requires binding to HS and angiotensin converting enzyme 2 (ACE2) in a codependent manner. Here, we show that commensal host bacterial communities can modify HS and thereby modulate SARS-CoV-2 spike protein binding and that these communities change with host age and sex. Common human-associated commensal bacteria whose genomes encode HS-modifying enzymes were identified. The prevalence of these bacteria and the expression of key microbial glycosidases in bronchoalveolar lavage fluid (BALF) was lower in adult COVID-19 patients than in healthy controls. The presence of HS-modifying bacteria decreased with age in two large survey datasets, FINRISK 2002 and American Gut, revealing one possible mechanism for the observed increase in COVID-19 susceptibility with age. In vitro, bacterial glycosidases from unpurified culture media supernatants fully blocked SARS-CoV-2 spike binding to human H1299 protein lung adenocarcinoma cells. HS-modifying bacteria in human microbial communities may regulate viral adhesion, and loss of these commensals could predispose individuals to infection. Understanding the impact of shifts in microbial community composition and bacterial lyases on SARS-CoV-2 infection may lead to new therapeutics and diagnosis of susceptibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/238444v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@14ff1ecorg.highwire.dtl.DTLVardef@193d84corg.highwire.dtl.DTLVardef@15d6f9eorg.highwire.dtl.DTLVardef@14b16c6_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract. Diagram of hypothesis for bacterial mediation of SARS-CoV-2 infection through heparan sulfate (HS).It is well known that host microbes groom the mucosa where they reside. Recent investigations have shown that HS, a major component of mucosal layers, is necessary for SARS-CoV-2 infection. In this study we examine the impact of microbial modification of HS on viral attachment. C_FIG

Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults.

Background Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated. Methods and Results The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex-specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all-cause deaths were recorded during a median follow-up of 10 years. Hazard ratios for all-cause death presented J- or U-shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone. Conclusions A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death.